An assay has been developed in which the DNA repair deficiency of the human genetic disease Xeroderma Pigmentosum is transiently complemented by the introduction by microinjection of cytoplasmic poly(A)+RNA derived from HeLa cells. This assay will be utilized to isolate and clone a cDNA copy of the repair mRNA. The cDNA copy will be used as a probe to identify a clone containing the genomic copy of the repair gene from a human, recombinant DNA library. Structural analyses of the cloned genes and biochemical characterization of their expression products will be performed. These studies should help to elucidate the molecular mechanisms of human, DNA excision repair and the pathobiology of XP. In addition, studies on the feasibility of effecting DNA-mediated transformation of mutant cell lines by direct microinjection of recombinant DNA libraries will be performed. Methods for the selection and rescue of single-copy eucaryotic genes from transformed clones are detailed.